Everyone is raving about male birth control — here's when it might actually arrive

Women get a short and complicated stick when it comes to family
planning.

Though birth control pills are 99% effective when taken
correctly,
free in the US, and among the safest and most widely used
forms of contraception, there's a lot to dislike, namely the
common side effects.

A lot of women on the pill or other hormone-based forms of birth
control report experiencing acne, mood swings, depression,
cramping, nausea, vomiting, breast tenderness, bleeding between
periods, weight gain, and changes in sexual desire, to name a few
things. Some formulations can even lead to serious complications
(though very rarely) like blood clots, heart attack, stroke,
liver tumors, and gallstones,
according to Planned Parenthood.

Meanwhile, men don't have any FDA-approved pill, patch, implant,
shot, or other medicated form of birth control available to them.
The only safe and effective options are condoms, vasectomies
(which aren't easily reversible), or abstinence. (Sorry, guys,
pulling out is
a very risky strategy.)

If some oral or injectable drug could safely, reliably, and
temporarily reduce a man's sperm fertility, then family
planning options could be more balanced — and millions of women
could breathe huge sighs of relief.

Thus the world
is in a tizzy over a new study of a male birth control
injection, which reliably slowed down sperm production to a
crawl.

The research, published October 27
in The Journal of Clinical Endocrinology and Metabolism, focused
on 320 male volunteers in steady relationships with women.
Researchers injected the guys with a two-hormone cocktail, which
was designed to suppress sperm formation, every two months for 13
months.

The injection was about 98% effective in preventing unwanted
pregnancies in the portion of men who responded to the hormones.
Furthermore, this clinical infertility reversed within a year
after stopping injections for about 95% of volunteers.

As good as this may sound on paper, however, it may be years
before it makes its way to apothecaries or doctors' offices.

The reason? A hodgepodge of cultural, bureaucratic, and
scientific issues stand in the way.

How the injection works

Thomson
Reuters

Most birth control methods for women exploit a natural moment of
infertility,
and reversibly so: pregnancy.

By regularly taking the pill, which contains synthetic versions
of pregnancy hormones (like estradiol, a progestin, or both),
women can prevent ovulation, hinder implantation of a fertilized
egg, block sperm from reaching their eggs, or all
three.

The new male birth control injection works a different route: by
cutting sperm production down to levels less than 1 million sperm
per milliliter, which are considered clinically infertile. (The
typical
fertile man, according to the World Health Organization, has
about 15 million sperm per milliliter of semen, or 39 million
sperm per ejaculation.)

The injection uses two different synthetic hormones to get the
job done.

The other hormone is a synthetic form of testosterone. Though
testosterone does a lot in the bodies of both men and women, it's
best known for its boost to sex drive
in men. But too much, as researchers learned in the 1980s and
1990s,
can slow down sperm production — and so testosterone became a
prime target for male birth control.

Getting the dose correct emerged
as one issue, though. While one concentration of testosterone
would slow sperm production in one man, it would not for another,
and inconsistency is something no one likes in their drugs. The
new study also notes there are concerns about significant
long-term side effects for taking high doses of synthetic
testosterone.

Luckily, scientists in the mid-2000s discovered that mixing
progestogens and testosterone provided a double-whammy to sperm
production, all while requiring less testosterone.

Trouble is, it wasn't known how well the injection and reduced
sperm counts would work in the real world: during unprotected
sex.

What the new study discovered

The new study, penned by 16 researchers from all over the world,
ran from 2008 through 2012 in three phases.

Their idea was to test how regular progestogen-testosterone
injections worked on stable heterosexual couples who voluntarily
went off birth control.

Researchers set up 10 sites in seven different countries to
recruit men "aged 18-45 years, and their 18-to-38-year-old female
partners, in stable, monogamous relationships," according to the
study. Volunteers were told there was a risk for pregnancy, too,
since the procedure was experimental.

The researchers ended up enrolling 320 male volunteers in the
first "suppression" phase: a round of four injections over 24
weeks, which shut down sperm production to 1 million cells per
milliliter (or less).

At least seven men (2%) didn't see suppressed sperm production,
while dozens of other men dropped out. This left 266 volunteers
who responded and moved on to the second "efficacy" phase. Men
received injections once every 8 weeks for 56 weeks and didn't
use condoms — all while their girlfriends or wives went off birth
control.

Due to a big and unexpected change in the study (more on this
later), plus additional dropouts, the researchers ended up with
111 men who fully completed this crucial phase.

Six men "rebounded" above of the 1-million-sperm cutoff over the
56-week period, and four couples got pregnant. If you
compare those pregnancies to all the time couples spent on male
birth control — again, not in combination with any female
contraception — it was about 97-98% effective. That's
pretty close to the 99% effectiveness seen with correct use of
the pill for women.

But the researchers also tested a big concern for male birth
control: a return to fertility.

Nearly 95% of men who received the injections bounced back to the
study's measure of a fertile sperm count within a year. On
average, it took about half a year for the volunteers to spring
back in this third "recovery" phase of the study.

But eight men had trouble resuming fertile sperm counts. It took
five of them longer than a year to recover, with at least one man
taking 74 weeks. One man didn't recover fertile sperm counts
within 4 years after his last injection, though it's impossible
to know if the injections or some other problem led to that
result.

"It shows that it's a risk, a low-probability risk of it, and
it's not to be sneezed at as a risk of it, surely," said
Elisabeth Lloyd, a faculty scholar at the Kinsey Institute,
professor of biology and an adjunct professor of philosophy at
Indiana University Bloomington. She is unaffiliated with the new
study.

That was just one issue with the study, though.

Counting the caveats

No study is perfect, and this one had plenty of complications
that are important to consider.

For one, a sample size of 320 men — while seemingly large — is
not as ideal as studying, say, 5,000 or even 1,000 men. And
again, the injections didn't work on some men, and a lot of men
dropped out of the study.

Second, if you live in the US you may be surprised to know that
all 10 of the study's recruiting centers were out of the country.
Two sites each were located in "Australia, Germany, and United
Kingdom and 1 site [each] in Chile, India, Indonesia, and Italy,"
according to the study.

Third, the requirements that men had to fulfill to be included in
the study were strict. They included:

a sperm count of 15 million per milliliter, or 39 million per
ejaculation (in two separate samples)

no sperm abnormalities or other problems

typical hormone levels

no serious diseases, psychiatric or otherwise

no signs of a sexually transmitted disease, either currently
or in the past

"a stable, mutually monogamous partnership for at least 1 year
was required, along with a coital frequency of twice/week on
average, an intent to remain in the relationship for the course
of the study, no desire for pregnancy within the next 2 years,
and willingness to accept a low but unknown risk of pregnancy."

Another huge caveat was a major interruption of the study about 3
years in.

By late 2010, the side effects were becoming apparent; for
example, about 46% of men reported getting acne; 23% said the
injection site hurt, and 16% experienced muscle pain. (If you're
one of the
4.5% of American women who get injectable birth control, such
side effects may seem all too
familiar.)

There were also more serious side effects that were at least
"possibly" related to the injections, including "reports of mood
changes, depression, pain at the injection site, and increased
libido," the researchers wrote in their study.

Two external boards of reviewers met frequently to go over the
study's data and determine, ethically, if it should continue.

One review board in January 2011 told the researchers that they
could keep going.

In March 2011, however, the other review board told the
researchers to stop injections and move on to the recovery phase.
In particular, 3% of men in the study who said they experienced
depression troubled the latter review board.

For context, compare that the 30% of women who report
depression (plus other side effects) on female birth control, as
Lloyd told CNN. (Yes,
that rate is 10 times higher.)

In their study, the researchers didn't seem pleased with the
second board's decision:

"It is well known from other trials of hormonal regimens in men
[...] that [adverse events] are reported frequently in these
longterm studies, even in a placebo group. That being said, 2
independent safety committees [...] came to different conclusions
on the safety of the regimen, which resulted in early termination
of the study injections."

Because of that interruption, plus the fact that you can't
ethically give study volunteers a placebo or "fake" injection (a
lot of unplanned pregnancies would happen), "a definitive
answer as to whether the potential risks of this hormonal
combination for male contraception outweigh the potential
benefits cannot be made based on the present results,"
they wrote (our emphasis added).

Still, the study's authors said their work shows promise.

In addition to being effective, they noted more than 75% of
couples wanted to continue using the injections instead of female
birth control.

Male birth control is not 'here' — yet

Gene
Kim

Some outlets have teased that male birth control is here or
"almost
here." And while it certainly seems within reach, it has been
a strange uphill battle — one that's likely years away from any
kind of conclusion.

Until recently, most research into male birth control has focused
on animals like rodents. The results have been mixed, with some
early successes failing to translate to humans.

One reason for the dearth of research into male contraceptives is
that men have no known, natural cycle of infertility. In short,
the testicles are "always on" and making sperm, and well into old
age; pregnancy in women seemed like a more natural target for
contraception.

Pharmaceutical companies should also accept some responsibility
for the slow pace. Even where certain male contraceptives showed
promise, for-profit ventures pulled their funding, presumably to
maintain a lucrative status quo, according to a 2008
study.

The cost to develop and test a drug is also steep, typically
hundreds of millions of dollars or sometimes billions, and
it's no guarantee — it can fail FDA approval. In fact, about
86% of drugs don't pass the FDA's final two approval stages.
(And that's before considering the fact that 94% of all drugs
that pass initial animal trials fail to pass any of the three
human clinical trials.) Even if a drug does pass, it can show
weak results or turn up potential side effects that consumers
won't be willing to risk in a medication.

So unless the injection passes future clinical drug trials to
show it's safe and effective for a much larger and more diverse
population, the first male birth control is unfortunately still a
ways off.

Should progestogen-testosterone shots succeed, they may not be
enough to help all men:

"No single method is used universally by all women; in a way this
is analogous to the less than 5% of men who may not adequately
suppress their sperm output," the author of one 2008 review of male
birth control research wrote. "The need for a range of
different options is obvious because no single method can be
expected to be ideal for every couple."